RESUMEN
AIMS: Self-monitoring of blood glucose (SMBG) represented a major breakthrough in the treatment of type 1 diabetes. The aim of the present meta-analysis is to assess the effect of continues glucose monitoring (CGM) and flash glucose monitoring (FGM), on glycemic control in type 1 diabetes. MATERIALS AND METHODS: The present analysis includes randomized clinical trials comparing CGM or FGM with SMBG, with a duration of at least 12 weeks, identified in Medline or clinicaltrials.gov. The principal endpoint was HbA1c at the end of the trial. A secondary endpoint was severe hypoglycemia. Mean and 95% confidence intervals for HbA1c and Mantel-Haenzel odds ratio [MH-OR] for severe hypoglycemia were calculated, using random effect models. A sensitivity analysis was performed using fixed effect models. In addition, the following secondary endpoints were explored, using the same methods: time in range, health-related quality of life, and treatment satisfaction. Separate analyses were performed for trials comparing CGM with SMBG, and those comparing CGM + CSII and SMBG + MDI and CGM-regulated insulin infusion system (CRIS) and CSII + SMBG. RESULTS: CGM was associated with a significantly lower HbA1c at endpoint in comparison with SMBG (- 0.24 [- 0.34, - 0.13]%); CGM was associated with a significantly lower risk of severe hypoglycemia than SMBG. Treatment satisfaction and quality of life were not measured, or not reported, in the majority of studies. FGM showed a significant reduction in the incidence of mild hypoglycemia and an increased treatment satisfaction, but no significant results are shown in HbA1c. CGM + CSII in comparison with SMBG + MDI was associated with a significant reduction in HbA1c. Only two trials with a duration of at least 12 weeks compared a CRIS with SMBG + CSII; HbA1c between the two treatment arms was not statistically significant (difference in means: - 0.23 [- 0.91; 0.46]%; p = 0.52). CONCLUSION: GCM compared to SMBG has showed a reduction in HbA1c and severe hypoglycemia in patient with type 1 diabetes. The comparison between CGM + CSII and SMBG + MDI showed a large reduction in HbA1c; it is conceivable that the effects of CSII + CGM on glycemic control additives. The only comparison available between FGM and SMBG was conducted in patients in good control.
Asunto(s)
Glucemia/análisis , Diabetes Mellitus Tipo 1/sangre , Control Glucémico , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricos , Adulto , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Automonitorización de la Glucosa Sanguínea/instrumentación , Automonitorización de la Glucosa Sanguínea/métodos , Automonitorización de la Glucosa Sanguínea/estadística & datos numéricos , Sistemas de Computación , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/epidemiología , Femenino , Hemoglobina Glucada/análisis , Hemoglobina Glucada/efectos de los fármacos , Hemoglobina Glucada/metabolismo , Control Glucémico/instrumentación , Control Glucémico/métodos , Control Glucémico/estadística & datos numéricos , Humanos , Hipoglucemia/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Insulina/administración & dosificación , Insulina/efectos adversos , Sistemas de Infusión de Insulina , Masculino , Calidad de VidaRESUMEN
AIM: To assess whether LC diets are associated with long-term improvement in glycemic control and weight loss in people with T2DM, and their cardiovascular and renal safety. METHODS: Meta-analysis of randomized controlled trials lasting more than 3 months, retrieved through extensive search on PubMed, Embase, ClinicalTrial.gov, Cochrane databases up to March 1st, comparing LC diets and balanced carbohydrate diets in people with T2DM. RESULTS: We retrieved 37 trials, including 3301 patients. Average carbohydrate intake in LC diets was 36% of total energy. LC diets were associated with significant reduction of HbA1c at 3 months (MD - 0.17%, 95% CI - 0.27, - 0.07), no difference at 6 and 12 months, and significant increase at 24 months (MD 0.23%, 95% CI MD 0.02, 0.44). VLC diets were associated with significant HbA1c reduction at 3 and 6 months (MD - 0.43% - 0.60, - 0.26%, and MD - 0.40% 95% CI - 0.59, - 0.22, respectively), but not at 12 and 24 months. LC diets were associated with significant BMI reduction at 6 months (- 1.35 kg/m2 95% CI, - 2.18, - 0.52), but not at other time points. Only a minority of trials reported data on renal function, so renal safety could not be assessed. No significant differences in body weight, lipid profile, or blood pressure were found in the long term. CONCLUSION: LC diets may produce small short-term improvements in HbA1c and weight, which are not maintained in the long term. Data on their renal safety are insufficient.
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Diabetes Mellitus Tipo 2/dietoterapia , Dieta Baja en Carbohidratos , Adulto , Anciano , Glucemia/metabolismo , Peso Corporal , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Riesgo , Pérdida de PesoRESUMEN
Dypeptidylpeptidase-4 (DPP-4) inhibitors are a therapeutic option for improving glucose control in patients with type 2 diabetes. They can be prescribed at different stages of the natural history of the disease because of their low risk for hypoglycemia and associated weight gain. For all new drugs for diabetes, the US Food and Drug Administration requires the demonstration of the cardiovascular (CV) safety profile through pooled analyses of phase 3 studies or specifically designed trials. A significant superiority over placebo has been observed with a sodium-dependent glucose transporter-2 inhibitor, empagliflozin, and two glucagon-like peptide-1 receptor agonists, liraglutide and semaglutide, thus suggesting cardioprotective effects for some antidiabetic drugs. The neutral results of CV safety trials on DPP-4 inhibitors have been disappointing, appearing to contradict the data from pooled analyses and meta-analyses of early trials. The main aim of this review is to find a possible interpretation for the differences between the results of these early trials and the CV safety studies with DPP-4 inhibitors. We conclude that the hypothesis of additional beneficial effects by DPP-4 inhibitors (beyond the improvement of glucose control), on the CV system in low-risk patients in primary prevention, needs to be verified with specifically designed studies.
Asunto(s)
Glucemia/efectos de los fármacos , Enfermedades Cardiovasculares/prevención & control , Sistema Cardiovascular/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Prevención Primaria , Biomarcadores/sangre , Glucemia/metabolismo , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/fisiopatología , Sistema Cardiovascular/fisiopatología , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiología , Inhibidores de la Dipeptidil-Peptidasa IV/efectos adversos , Humanos , Factores Protectores , Medición de Riesgo , Factores de Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND AND AIMS: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors determine a wide reduction of LDL cholesterol, greater than other lipid-lowering agents. The present meta-analysis is aimed at the assessment of PCSK9 inhibitors effect on LDL Cholesterol, cardiovascular morbidity and all-cause mortality. METHODS AND RESULTS: A Medline and Clinicaltrials.gov search for eligible studies until December 1, 2017, was performed. All randomized trials (> 12 weeks) comparing PCSK-9 inhibitors with placebo or active drugs were retrieved. Primary endpoints: (a) LDL cholesterol at endpoint; (b) Major cardiovascular events (MACE); (c) All-cause mortality. Data extraction was performed independently by two of the authors, and conflicts resolved by a third investigator. A total of 38 trials fulfilling the inclusion criteria were identified, with mean duration of 36.4 weeks. The reduction of LDL cholesterol at endpoint, versus placebo, ezetimibe, and high-dose statins was - 65.3 [- 69.6, - 60.9]%, - 57.7 [- 68.3;- 47.0]%, and - 34.5 [- 40.8;- 28.1]%, respectively, with alirocumab possibly showing a smaller effect than the other drugs of the class. Treatment with PCSK9 inhibitors was associated with a reduction in the incidence of MACE (Mantel-Haenszel Odds Ratio [MH-OR] 0.83 [0.78, 0.88]), with significant effects of alirocumab and evolocumab only. The number needed to treat for 2 years for preventing one event was 89. All-cause mortality and cardiovascular mortality were not reduced by treatment with PCSK-9 inhibitors (MH-OR 0.94 [0.84, 1.04] and 0.97[0.86;1.09]). CONCLUSIONS: PCSK-9 inhibitors are effective in reducing LDL cholesterol and the incidence of major cardiovascular events in high-risk patients. Bococizumab does not show significant effects on MACE. REGISTRATION NUMBER: PROSPERO-CRD42018087640.
Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticolesterolemiantes/uso terapéutico , Enfermedades Cardiovasculares/mortalidad , LDL-Colesterol/metabolismo , Inhibidores de PCSK9 , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/metabolismo , Humanos , Morbilidad , Pronóstico , Ensayos Clínicos Controlados Aleatorios como Asunto , Tasa de SupervivenciaRESUMEN
BACKGROUND: Degludec is a long-acting insulin with a longer duration of action and a greater day-to-day reproducibility of absorption in comparison with previous long-acting insulin formulations. The aim is the definition of the change in insulin needs in patients switching from detemir/glargine to degludec in real-life conditions. METHODS: In this retrospective cohort observational study, all outpatients with either type 1 or type 2 diabetes, starting therapy with degludec insulin-after a prior treatment with either detemir or glargine insulin for at least 6 months-were included. RESULTS: The analysis was performed on 266 patients, 172 and 96 with type 1 and type 2 diabetes, respectively. The equations describing the relationship between baseline and follow-up doses of basal insulin (6 months) were Y = 3.39 + 0.78X and Y = 0.44 + 0.69X, in patients receiving detemir/glargine either once or twice daily, respectively (Y = degludec dose at 6 months and X = basal insulin dose at switch). The corresponding equations for prandial insulin doses were y = 1.83 + 0.83*x and y = 2.85 + 0.80*x for those on pre-switch once or twice-daily basal insulin, respectively. In type 2 diabetes, the switch was associated with a reduction of basal insulin doses only in those with a prior twice-daily treatment with basal insulin. The reduction of prandial insulin reached statistical significance only in patients previously treated with basal insulin once daily. CONCLUSIONS: The present results provide a suggestion for a simple method for the adjustment of basal and prandial insulin doses in type 1 diabetic patients, switching from glargine or detemir to degludec.
Asunto(s)
Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Insulina Glargina/administración & dosificación , Insulina de Acción Prolongada/administración & dosificación , Adulto , Biomarcadores/análisis , Glucemia/análisis , Diabetes Mellitus Tipo 1/patología , Diabetes Mellitus Tipo 2/patología , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Hemoglobina Glucada/análisis , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios RetrospectivosRESUMEN
BACKGROUND & AIMS: Recently, the SAVOR TIMI-53 (Saxagliptin Assessment of Vascular Outcomes Recorded in patients with diabetes mellitus--Thrombolysis in Myocardial Infarction-53) reported a significant increase in the risk of hospitalizations for heart failure in patients treated with saxagliptin in comparison with placebo. Aim of the present meta-analysis is the systematic collection and synthesis of information on treatment-emergent cases of acute heart failure described in randomized clinical trials with DPP4. DATA SOURCES: An extensive Medline, Embase, and Cochrane Database search for "vildagliptin", "sitagliptin", "saxagliptin", "alogliptin", "linagliptin", and "dutogliptin" was performed, collecting all randomized clinical trials on humans up to October 1st, 2013. Studies were included if they satisfied the following criteria: i) randomized trials, ii) duration ≥24 weeks; iii) on type 2 diabetes; iv) comparison of DPP4i with placebo or active drugs. The principal outcome was the effect of DPP4i on the incidence of acute heart failure. A total of 84 eligible trials was identified. The overall risk of acute heart failure was higher in patients treated with DPP4i in comparison with those treated with placebo/active comparators (MH-OR: 1.19[1.03; 1.37]; p = 0.015). When trials with non-cardiovascular outcomes were analysed separately no signal of risk was detectable. CONCLUSION: Available data from RCTs suggest that DPP4i could be associated with an increased risk of heart failure, without any clear evidence of differences among drugs of the class. Although it is plausible that the risk is greater in some sub-populations of patients, current evidence is not yet sufficient to identify susceptible patients.
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Inhibidores de la Dipeptidil-Peptidasa IV/efectos adversos , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Insuficiencia Cardíaca/epidemiología , Enfermedad Aguda , Adamantano/efectos adversos , Adamantano/análogos & derivados , Adamantano/uso terapéutico , Bases de Datos Factuales , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Dipéptidos/efectos adversos , Dipéptidos/uso terapéutico , Insuficiencia Cardíaca/etiología , Hospitalización , Humanos , Incidencia , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de RiesgoRESUMEN
AIM: To assess hypoglycaemic risk with sulphonylureas in comparison with other drugs in randomized controlled trials. METHODS: Randomized trials with a duration ≥ 24 weeks, enrolling patients with type 2 diabetes, comparing sulphonylureas with placebo or active drugs different from other sulphonylureas. The principal outcome was the effect of sulphonylureas on the incidence of any or severe hypoglycaemia. Cumulative incidence of hypoglycaemia was estimated combining sulphonylurea groups of different trials with a random effect model and used for meta-regression analyses. RESULTS: The incidence of severe hypoglycaemia in patients treated with sulphonylureas was 1.2 [1.0-1.6]%. The overall risk of severe hypoglycaemia was increased more than threefold with sulphonylureas than with comparators. The proportion of patients with at least one hypoglycaemia while on sulphonylureas was 17.4 [14.5-20.8]%. The overall risk (Mantel-Haenszel Odds Ratio) of any hypoglycaemia with sulphonylureas versus comparators was 3.69 [3.47-3.93] (p < 0.001). Meta-regression analysis suggested that the incidence of any hypoglycaemia was higher in trials enrolling patients with higher body mass index (BMI) and lower haemoglobin A1c (HbA1c). CONCLUSIONS: In conclusion, hypoglycaemia, including severe hypoglycaemia, is frequent in patients treated with sulphonylureas, particularly when baseline HbA1c levels are lower and BMI levels higher. Further studies are needed to characterize predictors for the identification of patients at higher risk.
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Glucemia/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemia/inducido químicamente , Hipoglucemiantes/efectos adversos , Compuestos de Sulfonilurea/efectos adversos , Glucemia/efectos de los fármacos , Índice de Masa Corporal , Diabetes Mellitus Tipo 2/sangre , Hemoglobina Glucada/efectos de los fármacos , Hemoglobina Glucada/metabolismo , Humanos , Hipoglucemia/sangre , Hipoglucemia/prevención & control , Hipoglucemiantes/administración & dosificación , Incidencia , Oportunidad Relativa , Ensayos Clínicos Controlados Aleatorios como Asunto , Medición de Riesgo , Factores de Riesgo , Compuestos de Sulfonilurea/administración & dosificaciónRESUMEN
AIM: Some observational studies reporting an increased risk of pancreatitis in association with Dipeptidyl Peptidase-4 inhibitors (DPP4i) have raised concerns on the overall safety of this class. Aim of the present meta-analysis is the systematic collection of information on pancreatitis in randomized clinical trials with DPP4i. DATA SOURCES: an extensive Medline, Embase and Cochrane Database search for 'vildagliptin', 'sitagliptin', 'saxagliptin', 'alogliptin', 'linagliptin' and 'dutogliptin' was performed up to 1 March 2013. STUDY SELECTION: studies were included if they satisfied the following criteria: (i) randomized trials, (ii) duration ≥12 weeks, (iii) on type 2 diabetes and (iv) comparison of DPP4i with placebo or active drugs. The identification and the selection of studies, and the subsequent data extraction were performed independently by two authors. Mantel-Haenszel odds ratio with 95% Confidence Interval (MH-OR) was calculated for all the adverse events defined below. The principal outcome was the effect of DPP4i on the incidence of pancreatitis. RESULTS: A total of 134 eligible trials were identified. The overall risk of pancreatitis and pancreatic cancer was not different between DPP4i and comparators (MH-OR: 0.93[0.51-1.69]; p = 0.82). CONCLUSIONS: It should be recognized that the number of observed cases of incident pancreatitis is small and the confidence intervals of risk estimates are wide. However, the present meta-analysis do not suggest any increase in the risk of pancreatitis with DPP4i.
Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores de la Dipeptidil-Peptidasa IV/efectos adversos , Neoplasias Pancreáticas/inducido químicamente , Pancreatitis/inducido químicamente , Inhibidores de la Dipeptidil-Peptidasa IV/administración & dosificación , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Femenino , Humanos , Incidencia , Masculino , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de RiesgoRESUMEN
AIMS: New drugs for type 2 diabetes need to demonstrate their cardiovascular safety, due regulatory requirements from the Food and Drug Administration. For this reason, glucagon-like peptide-1 receptor agonists (GLP-1 RA) are currently undergoing large-scale, long-term randomized trials specifically designed for cardiovascular outcomes. Aim of the present meta-analysis of randomized clinical trials is the assessment of the effects of GLP-1 RA on major cardiovascular events (MACE), mortality and cardiovascular risk factors. METHODS: A meta-analysis was performed including all trials with a duration of at least 6 months, comparing a GLP-1 RA with a non-GLP-1 RA agent in type 2 diabetes. MACE and mortality were retrieved and combined to calculate Mantel-Haenzel odds ratio (MH-OR). Furthermore, data on endpoint systolic and diastolic blood pressure, total and high-density lipoprotein (HDL) cholesterol and triglyceride were collected. RESULTS: Of 37 selected trials, 33 reported information on MACE, and 25 reported at least one event. The difference in the incidence of MACE between GLP-1 RA and comparators did not reach statistical significance [MH-OR 0.78 (0.54-1.13), p = 0.18]. GLP-1 RA were associated with a significant reduction in the incidence of MACE in comparisons with placebo and pioglitazone, with a non-significant trend towards reduction in DPP4i-controlled studies. No significant effect of GLP-1 RA was observed on mortality, although a non-significant favourable trend was observed in comparisons with placebo. CONCLUSIONS: The present meta-analysis confirms the cardiovascular safety of GLP-1 RA, at least in the short term and in low-risk individuals. GLP-1 RA could have a beneficial effect on the incidence of MACE, at least in comparison with placebo.
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Enfermedades Cardiovasculares/inducido químicamente , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Péptido 1 Similar al Glucagón/análogos & derivados , Hipoglucemiantes/efectos adversos , Péptidos/efectos adversos , Receptores de Glucagón/agonistas , Ponzoñas/efectos adversos , Enfermedades Cardiovasculares/epidemiología , Diabetes Mellitus Tipo 2/sangre , Exenatida , Femenino , Péptido 1 Similar al Glucagón/administración & dosificación , Péptido 1 Similar al Glucagón/efectos adversos , Receptor del Péptido 1 Similar al Glucagón , Humanos , Hipoglucemiantes/administración & dosificación , Liraglutida , Masculino , Péptidos/administración & dosificación , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Riesgo , Ponzoñas/administración & dosificaciónRESUMEN
BACKGROUND: The reduction of hemoglobin A1c (HbA1c) levels is recognized as a useful means of preventing diabetic complications. HbA1c results from both fasting and post-prandial glycemia, and therefore FPG and PPG could provide different, and independent, contributions to long-term outcomes. Aim of the present meta-analysis is the assessment of the effects of reduction of FPG and PPG on cardiovascular outcomes in randomized controlled trials. METHODS: An extensive search of Medline was performed for all randomized trials with a duration of at least 52 weeks and performed on glucose-lowering agents. Differences in the incidence of cardiovascular events, and all-cause and cardiovascular mortality were assessed in trials comparing different treatments with a between-group difference in FPG or PPG at endpoint greater than 1 mmol/l. RESULTS: The Mantel-Haenszel Odds Ratio (MH-OR) for cardiovascular events and all-cause and cardiovascular mortality in patients on more intensive treatments, in trials with a between-group difference of PPG greater than 1 mmol/l, was not significantly different from controls (MH-OR [95%CI] 0.90 [0.51-1.58] for MACE); on the contrary, more intensive treatment of FPG produced a significantly lower all-cause (MH-OR 0.90 [0.81-0.99], p = 0.03) and cardiovascular (MH-OR 0.86 [0.76-0.97], p = 0.012) mortality, with no significant effect on the incidence of major cardiovascular events. CONCLUSIONS: In conclusion, reduction of FPG is associated with reduced cardiovascular mortality. Data on PPG are still scarce, but they point in the same direction.
Asunto(s)
Glucemia/análisis , Enfermedades Cardiovasculares/prevención & control , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 2/sangre , Angiopatías Diabéticas/prevención & control , Cardiomiopatías Diabéticas/prevención & control , Hiperglucemia/prevención & control , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/mortalidad , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Angiopatías Diabéticas/epidemiología , Angiopatías Diabéticas/mortalidad , Cardiomiopatías Diabéticas/epidemiología , Cardiomiopatías Diabéticas/mortalidad , Monitoreo de Drogas , Ayuno , Humanos , Hipoglucemiantes/uso terapéutico , Incidencia , Mortalidad , Periodo Posprandial , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
AIMS: Preliminary data from randomized trials with metabolic outcomes have shown that treatment with dipeptidyl peptidase-4 inhibitors (DPP4i) could be associated with a reduced incidence of major cardiovascular events (MACE). The present meta-analysis is aimed at verifying this protective effect, collecting all available data from randomized trials. METHODS: A comprehensive search for published and unpublished trials with a duration ≥24 weeks comparing DPP4i with placebo or other drugs was performed, retrieving all MACE reported as serious adverse events together with death from any cause. Mantel-Haenzel odds ratio (MH-OR) was calculated with random effect models for MACE, myocardial infarction, stroke and mortality. When available, effects on glycated haemoglobin, lipid profile and blood pressure were also assessed and used for the estimation of the modification of risk for myocardial infarction using the UKPDS risk engine. RESULTS: A total of 70 trials, enrolling 41 959 patients with a mean follow-up of 44.1 weeks, was collected and included in the analysis. The MH-OR (95% Confidence Interval) was 0.71[0.59;0.86], 0.64[0.44;0.94], 0.77[0.48;1.24] and 0.60[0.41;0.88] for MACE, myocardial infarction, stroke and mortality, respectively. CONCLUSIONS: Treatment with DPP4i reduces the risk of cardiovascular events (particularly myocardial infarction) and all-cause mortality in patients with type 2 diabetes. The reduction in the incidence of myocardial infarction is greater than what predicted on the basis of conventional risk factors, suggesting a role for other mechanisms.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Angiopatías Diabéticas/prevención & control , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Infarto del Miocardio/prevención & control , Accidente Cerebrovascular/prevención & control , Presión Sanguínea/efectos de los fármacos , Diabetes Mellitus Tipo 2/sangre , Angiopatías Diabéticas/sangre , Inhibidores de la Dipeptidil-Peptidasa IV/administración & dosificación , Femenino , Hemoglobina Glucada/efectos de los fármacos , Humanos , Incidencia , Metabolismo de los Lípidos/efectos de los fármacos , Masculino , Infarto del Miocardio/sangre , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Riesgo , Accidente Cerebrovascular/sangreRESUMEN
AIMS: Aim of this case-control study is the assessment of the relationship between antihypertensive treatment and incidence of diabetes in an unselected cohort of subjects participating in a screening program for diabetes. METHODS: A case-control study nested within a cohort of nondiabetic subjects with a mean follow-up of 27.7 ± 11.3 months was performed, comparing 40 cases of incident diabetes and 160 controls matched for age, sex, body mass index, fasting plasma glucose, 2-h post-load glycemia, smoking and alcohol abuse. RESULTS: When considering antihypertensive treatment at enrolment, a lower proportion of cases was exposed to ACE-inhibitors/angiotensin receptor blockers (ACE-i/ARB) in comparison with controls. A non-significant trend toward a higher exposure to diuretics, which were mainly represented by thiazide diuretics, was observed in cases. In a multivariate analysis, including both ACE-i/ARB and diuretics, a protective effect of ACEi/ARB, and an increased risk with diuretics were observed. Similar results were obtained in alternative models, after adjusting for systolic and diastolic blood pressure at enrolment, diagnosis of hypertension, concurrent treatment with ß-blockers or calcium-channel blockers, and number of antihypertensive medications. CONCLUSIONS: Diuretics seem to be associated with a higher incidence of diabetes, whereas treatment with ACEi/ARB could have a protective effect.
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Antihipertensivos/efectos adversos , Diabetes Mellitus/epidemiología , Hipertensión/tratamiento farmacológico , Adulto , Anciano , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antihipertensivos/farmacología , Antihipertensivos/uso terapéutico , Estudios de Casos y Controles , Estudios de Cohortes , Diabetes Mellitus/inducido químicamente , Diuréticos/efectos adversos , Diuréticos/uso terapéutico , Femenino , Estudios de Seguimiento , Humanos , Hipertensión/epidemiología , Incidencia , Masculino , Persona de Mediana EdadRESUMEN
AIM: To determine the association between the hypertriglyceridaemic waist phenotype, a combination of enlarged waist circumference and increased triglyceride levels, and ß-cell function in subjects with normal glucose tolerance and those with impaired glucose tolerance. METHODS: We studied 1344 outpatients clinic without diabetes. Overnight fasting blood samples were obtained to measure plasma glucose, insulin and lipids. An oral glucose tolerance test was performed in all subjects. All patients were divided in four groups, two groups with normal glucose tolerance and two with impaired glucose tolerance, with or without the hypertriglyceridaemic waist phenotype. Insulin resistance and ß-cell function were calculated by homeostatsis model assessment 2 indices. RESULTS: Twenty per cent of subjects showed the hypertriglyceridaemic waist phenotype and 23.8% had impaired glucose tolerance. We found a progressive significant increase (P < 0.001) of insulin resistance from subjects with normal glucose tolerance without the hypertriglyceridaemic waist phenotype with respect to patients with impaired glucose tolerance with the hypertriglyceridaemic waist phenotype. In subjects with normal glucose tolerance, the hypertriglyceridaemic waist phenotype was associated with a mild, but not significant, increase of homeostatsis model assessment 2-ß levels; but, in patients with impaired glucose tolerance, the hypertriglyceridaemic waist phenotype was associated with significantly lower homeostatsis model assessment 2-ß levels [127.0 (103.0-162.7) vs. 123.0 (96.0-147.0); P < 0.05]. The hypertriglyceridaemic waist phenotype displayed a higher (odds ratio 95% CI) ß-cell dysfunction of 1.8 (1.3-2.6) and insulin resistance of 5.0 (2.7-8.5) compared with 1.3 (0.9-1.9) and 2.4 (1.8-3.2), respectively, of waist circumference alone. CONCLUSION: In this study, the hypertriglyceridaemic waist phenotype is associated with increased insulin resistance and an overstimulation of ß-cell function in subjects with normal glucose tolerance, while patients with impaired glucose tolerance with the hypertriglyceridaemic waist phenotype showed a reduction in ß-cell function. These data suggest the importance of the identification of patients with impaired glucose tolerance combined with the hypertriglyceridaemic waist phenotype for an early intervention in relation to the high risk of developing Type 2 diabetes.
Asunto(s)
Diabetes Mellitus Tipo 2/metabolismo , Angiopatías Diabéticas/metabolismo , Intolerancia a la Glucosa/sangre , Hipertrigliceridemia/metabolismo , Resistencia a la Insulina , Células Secretoras de Insulina/metabolismo , Circunferencia de la Cintura , Adulto , Biomarcadores/sangre , Glucemia/metabolismo , Índice de Masa Corporal , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/fisiopatología , Angiopatías Diabéticas/sangre , Angiopatías Diabéticas/genética , Angiopatías Diabéticas/fisiopatología , Femenino , Intolerancia a la Glucosa/genética , Intolerancia a la Glucosa/metabolismo , Intolerancia a la Glucosa/fisiopatología , Humanos , Hipertrigliceridemia/sangre , Hipertrigliceridemia/genética , Hipertrigliceridemia/fisiopatología , Técnicas In Vitro , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Fenotipo , Factores de Riesgo , Triglicéridos/sangreRESUMEN
AIM: The reduced levels of glucagon-like peptide 1 (GLP-1) after an oral glucose load in Type 2 diabetic patients could be dependent either on a reduced synthesis or an increased degradation; but GLP-1 and dipeptidyl peptidase IV (DPP-IV) levels during an oral glucose tolerance test (OGTT) have not been studied together. The aim of the present study was to investigate GLP-1 and DPP-IV levels during an OGTT in patients with different degrees of glucose tolerance. METHODS: Fifty six subjects (34 female, 22 male) matched for sex, age, body mass index (BMI) and waist circumference underwent a 75 g oral glucose tolerance test. Twenty-eight had normal glucose tolerance, 15 had impaired glucose tolerance and 13 had Type 2 diabetes mellitus. GLP-1 assay was performed with an ELISA kit, and DPP-IV assay using a colorimetric method. RESULTS: At 30 min GLP-1 levels were significantly lower in subjects with impaired glucose tolerance and type 2 diabetes mellitus compared to those with normal glucose tolerance. The area under the GLP-1 curve was significantly different among the three groups; there was a significant decrease between subjects with normal and impaired glucose tolerance(P = 0.004) and between those with normal glucose tolerance and type 2 diabetes mellitus. (P < 0.001), while the area under the curve for DPP-IV showed no significant difference between the groups. CONCLUSIONS: These results suggest that an increase of GLP-1 degradation does not play a role in the early stages of diabetes mellitus.
Asunto(s)
Diabetes Mellitus Tipo 2/metabolismo , Dipeptidil Peptidasa 4/metabolismo , Péptido 1 Similar al Glucagón/metabolismo , Anciano , Área Bajo la Curva , Índice de Masa Corporal , Ayuno/metabolismo , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Masculino , Persona de Mediana Edad , Circunferencia de la CinturaRESUMEN
BACKGROUND: The impaired response of glucagonlike peptide-1 (GLP-1) to meals in diabetic patients can contribute to the pathogenesis of impaired insulin secretion and post-prandial hyperglycemia. This study is aimed at the assessment of the relationship between meal-induced GLP-1 and post-prandial hyperglycemia in Type 2 diabetic patients. METHODS: Twenty-one drug-naïve Type 2 diabetic patients were studied. Blood glucose and active GLP-1 levels were measured 0, 30, 60, 90, and 120 min after a standard test meal. A continuous glucose monitoring (CGM) system was applied for the following 3 days. Nutrient intake at each meal was calculated on the basis of patients' food records. For each patient, post-prandial 120-min glucose incremental area under the curve (iAUC) was included in linear regression model exploring its relationship with total energy and carbohydrate intake, and the angular coefficient for total energy (EAC) and carbohydrate (CAC) was calculated. RESULTS: GLP-1 levels peaked 30 min after the test meal. Logarithmically transformed 60-min GLP-1 iAUC showed a significant inverse correlation with glycated hemoglobin (HbA1c) (p<0.01). A significant inverse correlation of 60-min GLP-1 iAUC was also observed with EAC and CAC (both p<0.01), meaning that patients with a lower GLP-1 response to the test meal had a higher increment of post-prandial glucose for each additional unit of total energy or carbohydrate intake. CONCLUSIONS: In Type 2 diabetic patients, a lower GLP-1 response to meals is associated with a higher HbA1c, and with a greater degree of meal-induced hyperglycemia, both in a meal test and during CGM in "real-life" conditions.
Asunto(s)
Glucemia/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Ingestión de Alimentos/fisiología , Péptido 1 Similar al Glucagón/metabolismo , Hiperglucemia/metabolismo , Periodo Posprandial/fisiología , Área Bajo la Curva , Automonitorización de la Glucosa Sanguínea , Femenino , Péptido 1 Similar al Glucagón/sangre , Hemoglobina Glucada/metabolismo , Humanos , Modelos Lineales , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: The International Diabetes Federation (IDF) proposed to modify the diagnostic criteria for metabolic syndrome (MS) previously issued by the National Cholesterol Education Program (NCEP). Aim of the present investigation is to compare the predictive value for diabetes of NCEP and IDF definitions of MS in a large sample of predominantly Caucasian subjects. METHODS: A prospective observational study was performed on a cohort study (n = 3096) enrolled in a diabetes-screening programme, the FIrenze-Bagno A Ripoli study. All subjects with fasting glucose >126 mg/dl and/or post-load glucose > or =200 mg/dl (5.7%) were excluded from the present analysis. Follow-up of each subject was continued until diagnosis of diabetes, death or until 31 December 2005. Mean follow-up was 27.7 +/- 11.3 months. RESULTS: Among subjects enrolled, 13.7 and 25.2% were affected by MS using NCEP and IDF criteria respectively. During follow-up, 38 new cases of diabetes were diagnosed, with a yearly incidence rate of 0.5%. The relative risk for diabetes in subjects with MS was 10.10 [5.13; 20.00] and 7.87 [3.70; 16.7] using NCEP and IDF definitions respectively. After adjustment for age, sex, fasting glucose and waist circumference, NCEP-defined MS, but not IDF-, was significantly associated with incident diabetes (hazard ratio, 95% CI: 2.41 [1.01; 5.95] and 2.05 [0.80; 5.29] respectively). CONCLUSIONS: Although the reasons for the proposed changes in diagnostic criteria for MS are easily understandable, the newer IDF definition, while increasing estimates of prevalence of the syndrome, reduces the effectiveness of MS in identifying subjects at risk for diabetes. Further research is needed before the previous NCEP criteria are abandoned.
Asunto(s)
Diabetes Mellitus Tipo 2/epidemiología , Síndrome Metabólico/diagnóstico , Adulto , Anciano , Glucemia/metabolismo , Constitución Corporal , Diabetes Mellitus Tipo 2/sangre , Métodos Epidemiológicos , Femenino , Humanos , Italia/epidemiología , Lípidos/sangre , Masculino , Síndrome Metabólico/sangre , Síndrome Metabólico/epidemiología , Persona de Mediana Edad , PronósticoRESUMEN
This randomized, open-label, cross-over study compares the efficacy of mealtime rapid-acting analog insulin aspart with human insulin, in combination with metformin. A total of 30 patients with type 2 diabetes, inadequately controlled (HbA(1c)>7.5%) with oral hypoglycemic agents (OHAs), were assigned to human insulin 30 min before meals or aspart immediately before meals, both with metformin 500 mg t.i.d. for 90 days. Patients then switched to the alternate insulin. At 90 and 180 days, blood glucose and lipids were measured at baseline and every 30 min after test meals, for 3h. HbA(1c) and hypoglycemic events were also assessed. After 3 months, HbA(1c) was significantly reduced with aspart, but not human insulin (-0.4+/-0.7% versus +0.1+/-0.7%, p<0.05). During meal tests, blood glucose area under the curve (AUC) was significantly lower with aspart than human insulin (1240+/-476 min/mmol/l versus 1588+/-766 min/mmol/l, p<0.01). AUCs for lipids were similar for both treatments. Neither group experienced serious hypoglycemic events. These results encourage treatment with mealtime insulin aspart plus metformin, in type 2 diabetes patients with postprandial hyperglycemia inadequately controlled by OHAs alone.
Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Insulina/análogos & derivados , Insulina/uso terapéutico , Metformina/uso terapéutico , Anciano , Glucemia/metabolismo , Estudios Cruzados , Esquema de Medicación , Quimioterapia Combinada , Ingestión de Alimentos , Femenino , Humanos , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/uso terapéutico , Insulina/administración & dosificación , Insulina Aspart , Masculino , Persona de Mediana EdadRESUMEN
Metformin has been shown to increase glucagon-like peptide-1 (GLP-1) levels after an oral glucose load in obese non-diabetic subjects. In order to verify if this effect of the drug was also present in obese Type 2 diabetic patients who have never been treated with hypoglycemic drugs, 22 Type 2 diabetic and 12 matched non-diabetic obese patients were studied. GLP-1 was measured before and after a 100 g glucose load at baseline, after a single oral dose of 850 mg of metformin, and after 4 weeks of treatment with metformin 850 mg three times daily. Post-load GLP-1 levels were significantly lower in diabetic patients. A single dose of metformin did not modify GLP-1 levels. After 4 weeks of treatment, fasting GLP-1 increased in diabetic patients (3.8 vs 4.9 pmol/l; p<0.05), while the incremental area under the curve of GLP-1 significantly increased in both diabetic [93.6 (45.6-163.2) vs 151.2 (36.0-300.5) pmol x min/l; p<0.05] and non-diabetic [187.2 (149.4-571.8) vs 324.0 (238.2-744.0) pmol x min/l; p<0.05] subjects. In conclusion, GLP-1 levels after an oral glucose load in obese type 2 diabetic patients were increased by 4 weeks of metformin treatment in a similar fashion as in obese subjects with normal glucose tolerance.